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依赖青蒿琥酯通过长链非编码 RNA-RP11 抑制肝癌上皮间质转化。

Dependence of artesunate on long noncoding RNA-RP11 to inhibit epithelial-mesenchymal transition of hepatocellular carcinoma.

机构信息

Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan, China.

Department of Biochemistry, Medical School, Anhui University of Science and Technology, Huainan, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):6026-6034. doi: 10.1002/jcb.27889. Epub 2018 Oct 18.

Abstract

As a first line medicine for malaria treatment, artesunate (ART) also shows antitumor potential. However, little is known about the effect of ART on the cancer cell epithelial-mesenchymal transition (EMT). In this study, we found that ART inhibited cell growth in SK-HEP1 and SM7721 hepatocellular carcinoma cell lines. A microarray was used to identify differentially expressed protein-coding RNAs (pcRNA) and long noncoding RNAs (lncRNA) between SK-HEP1 cells with and without ART treatment. A differentially expressed lncRNA-RP11, the most related to the EMT of liver cancer cells-RP11 was identified by abioinformatics method Overexpressing and silencing assays were used to verify the role of RP11 in cancer cell EMT. The levels of RP11- and EMT-related genes in liver cancer samples from 75 patients were detected by using qualitative polymerase chain reaction or immunohistochemistry. We identified 1334 pcRNAs and 1670 lncRNA with differential expression induced by ART. ART inhibits EMT, proliferation, migration, invasion, and adhesion of liver cancer cells. RP11 depresses the inhibitory effect of ART on cancer cell EMT. The level of RP11 is associated with cancer cell EMT and metastasis and survival rate of the patient. These data suggest that RP11-linking ART and cancer cell EMT are important for ART-inhibited metastasis of liver cancer.

摘要

青蒿琥酯(ART)作为治疗疟疾的一线药物,也具有抗肿瘤潜力。然而,ART 对癌细胞上皮-间充质转化(EMT)的影响知之甚少。在本研究中,我们发现 ART 抑制了 SK-HEP1 和 SM7721 肝癌细胞系的细胞生长。通过微阵列鉴定了 ART 处理前后 SK-HEP1 细胞中差异表达的蛋白编码 RNA(pcRNA)和长链非编码 RNA(lncRNA)。通过生物信息学方法鉴定出最与肝癌细胞 EMT 相关的差异表达 lncRNA-RP11。通过过表达和沉默实验验证了 RP11 在癌细胞 EMT 中的作用。通过定性聚合酶链反应或免疫组织化学检测了 75 例肝癌患者肝癌样本中 RP11 和 EMT 相关基因的水平。ART 诱导的差异表达 pcRNA 为 1334 个,lncRNA 为 1670 个。ART 抑制 EMT、肝癌细胞的增殖、迁移、侵袭和黏附。RP11 抑制了 ART 对癌细胞 EMT 的抑制作用。RP11 的水平与癌细胞 EMT 和转移以及患者的生存率有关。这些数据表明,RP11-ART 和癌细胞 EMT 之间的联系对于 ART 抑制肝癌转移很重要。

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